Polymers in Pharmaceutical Drug Delivery System: A Review

Int. J. Pharm. Sci. Rev. Res.
, 14(2), 2012; nᵒ 10, 57‐66 ISSN 0976 – 044X
Review Article

POLYMERS IN PHARMACEUTICAL DRUG DELIVERY SYSTEM: A REVIEW

Krushnakumar J Gandhi*, Subhash V Deshmane, Kailash R Biyani
Department of Pharmaceutics, Anuradha College of Pharmacy, Chikhli, Dist‐ Buldana 443201, India.
*Corresponding author’s E‐mail: kjg16@rediffmail.com

Accepted on: 10‐04‐2012; Finalized on: 25‐05‐2012.
ABSTRACT
The current review article focuses on polymers in pharmaceutical drug delivery of therapeutic agents. These dosage forms include
tablets, patches, tapes, films, semisolids and powders. Polymers are the backbone of a pharmaceutical drug delivery system as they
control the release of the drug from the device. Biodegradable polymers attracts the attention of its use as they can be degraded to
non‐toxic monomers and most important, a constant rate of drug release can be achieved from a biodegradable polymer based
controlled release device. Natural polymers can be used as the means of achieving predetermined rates of drug delivery and their
physico‐chemical characteristics with the ease of availability provide a platform to use it as a polymer for drug delivery systems.
Biodegradable polymers have been widely used in biomedical applications because of their known biocompatibility and
biodegradability. In the biomedical area, polymers are generally used as implants and are expected to perform long term service.
These improvements contribute to make medical treatment more efficient and to minimize side effects and other types of
inconveniences for patients. The main role of polymer is to protect drug from physiological environment and prolong release of drug
to improve its stability. The drug is release from polymer by diffusion, degradation and swelling. In addition to this review presents
characteristics and behaviours of plant derived and mucoadhesive polymers which are currently used in drug delivery.
Keywords: Polymers, excipients, synthetic polymer, natural polymer, sustained release, control release, mucoadhesion.
INTRODUCTION compartments. These technical development in drug

delivery/targeting approaches improve the efficacy of
Over the past decades research at the level of molecular
drug therapy thereby improve human health.3 Polymer
biology has unveiled the molecular basis for many
chemists and chemical engineers, pharmaceutical
diseases. New important technologies and concepts such
scientists are engaged in bringing out design predictable,
as recombinant DNA and gene therapy have provided
controlled delivery of bio active agents.4
tools for the creation of pharmaceuticals and methods
designed to specifically address such diseases. However Extensive Biodegradable polymers have been widely
progress towards the application of these medicines used in biomedical applications because of their known
outside of the laboratory has been considerably slow biocompatibility and biodegradability. In the biomedical
principally due to the lack of effective drug delivery area polymers are generally used as implants and are
systems that is mechanisms that allow the release of the expected to perform long term service. These
drug into the appropriate body compartment for the improvements contribute to make medical treatment
appropriate amount of time without seriously disrupting more efficient and to minimize side effects and other
the rest of the organism functionality. The application of types of inconveniences for patients.5
the polymeric materials for medical purposes is growing
The pharmaceutical applications of polymers range from
fast. Polymers have found applications in diverse
their use as binders in tablets to viscosity and flow
biomedical fields such as drug delivering systems,
controlling agents in liquids, suspensions and emulsions.
developing scaffolds in tissue engineering, implantation
Polymers can be used as film coatings to disguise/mask
of medical devices and artificial organs, prosthesis,
the unpleasant taste of a drug, to enhance drug stability
ophthalmology, dentistry, bone repair, and many other
and to modify drug release characteristics.
medical fields.1 Polymers have been used as a main tool
Pharmaceutical polymers are widely used to achieve taste
to control the drug release rate from the formulations.
masking; controlled release (e.g. extended, pulsatile and
Extensive applications of polymers in drug delivery have
targeted) enhanced stability and improved bioavailability.
been realized because polymers offer unique properties
Monolithic delivery devices are systems in which a drug is
which have not been attained by any other materials.
dispersed within a polymer matrix and released by
Advances in polymer science have led to the development
diffusion. The rate of the drug release from a matrix
of several novel drug delivery systems. A proper
product depends on the initial drug concentration and
consideration of surface and bulk properties can aid in
relaxation of the polymer chains which overall displays a
the designing of polymers for various drug delivery
sustained release characteristic.6, 7
applications.2 These newer technological development
include drug modification by chemical means carrier Simple manipulation of the water solubility of polymers,
based drug delivery and drug entrapment in polymeric by increasing their chain length through cross‐linking or
matrices or within pumps that are placed in desired by hydrophobising or hydrophilizing them with
International Journal of Pharmaceutical Sciences Review and Research Page 57

Available online at www.globalresearchonline.net

Int. J. Pharm. Sci. Rev. Res., 14(2), 2012; nᵒ 10, 57‐66 ISSN 0976 – 044X
copolymers and other groups yields a wealth of materials polymers at an industrial scale and the quick and total
with a wide spectrum of possible application. The solubilization of the pharmaceuticals for safe inoculation.
resulting materials are capable of a variety of drug‐ The optimization of these clinical tests (in terms of dosage
enhancing functions.8 and frequency) is still being evaluated today for a large
variety of products.11
Polymers are able to:
• Prolong drug availability if medicines are formulated as
hydrogels9 or microparticles.10
• Favourably alter bio distribution, if formulated into
dense nanoparticles.
• Enable hydrophobic drug administration if formulated
as micelles.
• Transport a drug to its usually inaccessible site of action
if formulated as gene medicines.
Figure 1: The families of polymer constructs called
• Make drugs available in response to stimuli. polymer therapeutics.
HISTORY ROLE OF POLYMER IN PHARMACEUTICAL DRUG
DELIVERY8
The use of polymers in the medical field is not a novelty ‐
natural polymers have been used as components of  Immediate release dosage forms
herbal remedies for centuries. When it comes to synthetic
 Tablets
polymers however the situation is very different. Because
polymer science is a relatively recent area of research Polymers have been used for many years as excipients in
synthetic water‐soluble polymers as macromolecular conventional immediate‐release oral dosage forms, either
drugs or as part of drug delivery systems related to to aid in the manufacturing process or to protect the drug
inoculation can be considered a modern achievement. from degradation upon storage. Microcrystalline cellulose
The first polymer‐drug conjugates appeared around 1955, is often used as an alternative to carbohydrates as
being mescaline‐N‐vinylpyrolidine conjugate one of the diluents in tablet formulations of highly potent low‐dose
first. drugs. Starch and cellulose are used as disintegrants in
tablet formulations, which swell on contact with water,
About ten years later Frank Davis and Abraham
resulting in the tablet “bursting,” increasing the exposed
Abuchowski were able to foresee the potential of
surface area of the drug and improving the dissolution
conjugating poly(ethylene glycol) (PEG) to proteins
characteristics of a formulation. Polymers including
causing the birth of a technique called PEGylation.
polyvinyl‐pyrrolidone and hydroxypropyl methylcellulose
PEGylation consists in the covalent bond of poly(ethylene
(HPMC) also find uses as binders that aid the formation of
glycol) polymer chains to another molecule usually a drug
granules that improve the flow and compaction
or a protein with therapeutic effects.
properties of tablet formulations prior to tableting.
In 1994, the first synthetic polymer‐drug conjugate (as Occasionally, dosage forms must be coated with a “non‐
shown in figure 1b) designed to treat cancer was clinically functional” polymeric film coating in order to protect a
tested. It consisted on an HPMA (N‐(2‐hydroxypropyl) drug from degradation, mask the taste of an unpalatable
methacrylamide) copolymer conjugate of doxorubicin. drug or excipients, or improve the visual elegance of the
Targeted release of anticancer agents can also be made formulation without affecting the drug release rate. 12
using block copolymer micelles which have the ability to
 Capsules
entrap the drug or to covalently link to it.
Capsules are used as an alternative to tablets, for poorly
In the 2000s, two polymer‐protein conjugates,(as shown
compressible materials, to mask the bitter taste of certain
in figure 1a) PEG‐interferon‐α (an antiviral drug intended
drugs, or sometimes to increase bioavailability. Many of
to treat chronic hepatitis C and hepatitis B) and PEG‐GCSF
the polymeric excipients used to “bulk out” capsule fills
(PEG granulocyte colony‐stimulating factor) were placed
are the same as those used in immediate‐release tablets.
in the market and five years later the first therapeutic
Gelatine has been used almost exclusively as a shell
nanoparticles (albumin‐entrapped paclitaxel) was
material for hard (two‐piece) and soft (one‐piece)
approved as a treatment for metastatic breast cancer. All
capsules. HPMC has recently been developed and
the above achievements and researches were the core
accepted as an alternative material for the manufacture
element that led to the development of polymer based
of hard (two‐piece) capsules.
pharmaceuticals namely polymeric drugs, polymer‐drug
conjugates and polymer‐protein conjugates. The clinical  Modified‐release dosage forms
trials of these new technologies eventually lead to the
It is now generally accepted that for many therapeutic
resolution of many other unexpected challenges that
agents drug delivery using immediate release dosage
quickly appeared, such as the manufacturing of the

forms results in suboptimal therapy and/or systemic side processes including proliferation and differentiation. It

effects. Pharmaceutical scientists have attempted to has been shown that by careful selection of the polymer
overcome the limitations of conventional oral dosage and the processing method, controlled‐release matrices,
forms by developing modified release dosage forms. incorporating proteins and growth factors that induce and
enhance tissue growth can be produced. The future use
 Extended release dosage forms
of gene therapy as a way of regenerating tissue is an
The therapeutic effect of drugs that have a short exciting area, and despite still being in its infancy, it may
biological half‐life may be enhanced by formulating them yet provide a solution to the challenge of delivering drugs
as extended or sustained release dosage forms. Extended and proteins more effectively in all areas of medicine.
and sustained release dosage forms prolong the time that
Poly (lactic‐co‐glycolic acid) Microspheres
systemic drug levels are within the therapeutic range and
thus reduce the number of doses the patient must take to The term microsphere refers to a small sphere with a
maintain a therapeutic effect thereby increasing porous inner matrix and variable surface from smooth
compliance. The most commonly used water‐insoluble and porous to irregular and nonporous. The drug when
polymers for extended‐release applications are the encapsulated is dispersed throughout the inner matrix.
ammonium ethacrylate copolymers (Eudragit RS and RL), The size range of microspheres is typically 1 to 500 µm in
cellulose derivatives ethylcellulose, cellulose acetate, and diameter. Poly (lactic‐co‐glycolic acid) microspheres have
polyvinyl derivative, polyvinyl acetate. Eudragit RS and RL increasingly become the focus of research efforts in the
differ in the proportion of quaternary ammonium groups, scientific community and pharmaceutical industry. Their
rendering Eudragit RS less permeable to water, whereas application as drug delivery vehicles has risen in line with
ethylcellulose is available in a number of different grades the expanding biotechnology sector and the promise of
of different viscosity, with higher‐viscosity grades forming new drugs discovered in the wake of the human genome
stronger and more durable films. project and proteomics.
 Gastroretentive Dosage Forms Polymeric Nanoparticles as Drug Carriers
Gastroretentive dosage forms offer an alternative Certain chemical entities are either rapidly degraded
strategy for achieving extended release profile, in which and/or metabolized after administration (peptides,
the formulation will remain in the stomach for prolonged proteins, and nucleic acids). This is the reason the idea
periods, releasing the drug in situ, which will then that nanotechnologies may be employed to modify or
dissolve in the liquid contents and slowly pass into the even to control the drug distribution at the tissue,
small intestine. Unlike a conventional extended release cellular, or sub cellular levels has emerged. Among the
dosage form, which gradually releases the drug during technologies utilized for drug targeting are polymer‐
transit along the gastrointestinal tract, such a delivery based nanoparticles, which have been developed since
system would overcome the problems of drugs that are the early 1980s, when progress in polymer chemistry
absorbed preferentially from specific sites within the allowed the design of biodegradable and biocompatible
gastrointestinal tract (for example, many drugs are materials. Nanoparticles may be defined as being
absorbed poorly from the distal gut, where an extended‐ submicron (<1 µm) colloidal systems generally composed
release dosage form may spend the majority of its time), of polymers. Thus, nanoparticles are colloidal systems
producing nonuniform plasma time profile delivery with a size 7 to 70 times smaller than the red cells. They
systems do not relay on polymers present, to achieve may be administered intravenously without any risk of
gastroretention mucoadhesive13‐17 and low‐density18,19 embolization. Depending on the method used in the
polymers have been evaluated, with little success so far, preparation of nanoparticles, either nanospheres or
for their ability to extend gastric residence time by nanocapsules can be obtained. Nanospheres are matrix
bonding to the mucus lining of the stomach and floating systems in which the drug is dispersed within the polymer
on top of the gastric contents respectively. throughout the particle. On the contrary, nanocapsules
are vesicular systems, which are formed by a drug‐
TYPES OF POLYMER DRUG DELIVERY SYSTEM8
containing liquid core (aqueous or lipophilic) surrounded
Polymers for Drug Delivery in Tissue Engineering by a single polymeric membrane.
Several strategies have been developed in order to Polymeric Micelles as Pharmaceutical Carriers
regenerate functional tissue, the majority of which
Polymeric micelles demonstrate many attractive
involve the use of polymer scaffolds specifically designed
properties as pharmaceutical carriers. They are stable
to direct tissue growth. The cell transplantation method is
both in vitro and in vivo, can be loaded with a wide
one of the most commonly used in cartilage and bone
variety of poorly soluble pharmaceutical agents,
formation.20 Polymer matrices both natural and synthetic
effectively accumulate in pathological body areas with
can play a vital role in the delivery of protein growth
compromised vasculature (infarcts, tumors), and can be
factors and cytokines to aid angiogenesis and tissue
targeted by attaching various specific ligands to their
reconstruction procedures. These molecules are essential
surface. Both therapeutic and diagnostic micelles can be
to tissue growth as they control a number of vital cellular


easily produced in substantial quantities. It appears that Cellulose‐Based Polymers

micellar carriers have a promising future.
 Ethyl cellulose Insoluble but dispersible in water,
Polymeric Vesicles aqueous coating system for sustained release
applications.
Polymeric vesicles may be fabricated from a variety of
macromolecular amphiphile architectures, which include:  Carboxymethyl cellulose Super disintegrant, emulsion
block copolymers, random graft copolymers, and stabilizer.
polymers bearing hydrophobic low‐molecular‐weight
pendant or terminal groups. These tough particles, which  Hydroxyethyl and hydroxypropyl celluloses Soluble in
reside in the nanometre and micrometer size domains, water and in alcohol for tablet coating.
may be used for drug targeting, the preparation of  Hydroxypropyl methyl cellulose Binder for tablet
responsive release systems, and other drug delivery matrix and tablet coating, gelatin alternative as
applications. capsule material.
Polymer Drug Conjugates  Cellulose acetate phthalate enteric coating.
Current research in the field of polymer anticancer drug Hydrocolloids
conjugates is directed towards the identification of the
mechanism of action of free and polymer‐bound drugs at  Alginic acid Oral and topical pharmaceutical
the cellular and subcellular levels. Newer applications for products; thickening and suspending agent in a
polymer–drug conjugates are also being explored21. variety of pastes, creams, and gels, as well as a
Inflammatory diseases are characterized by an increase in stabilizing agent for oil‐in‐water emulsions; binder
the vascular permeability (similar to tumors). Though and disintegrants.
there may be lesser amounts of retention as the  Carrageenan Modified release, viscosifier.
lymphatics are not blocked, there may be a therapeutic
advantage offered by the conjugation of drugs to polymer  Chitosan Cosmetics and controlled drug delivery
backbones. These represent new and exciting avenues of applications, mucoadhesive dosage forms, rapid
research for polymeric drug delivery scientists. release dosage forms.
Polymers Used for the Delivery of Genes in Gene Water‐Insoluble Biodegradable Polymers
Therapy  (Lactide‐co‐glycolide) polymers Microparticle–
A number of polymers by virtue of possessing a cationic nanoparticle for protein delivery.
charge at physiological pH have been found to be suitable Starch‐Based Polymers
candidates for the transfer of genes across the various
biological barriers outlined in the preceding text. An ideal  Starch Glidant, a diluent in tablets and capsules,
gene delivery system has to be able to shuttle the gene a disintegrant in tablets and capsules, a tablet
safely to the nuclei of its target tissue with the travelling binder.
gene having limited encounters with degradative
 Sodium starch glycolate super disintegrant for
influences.
tablets and capsules in oral delivery.
POLYMERS IN PHARMACEUTICAL APPLICATIONS22‐24
Plastics and Rubbers
Water‐Soluble Synthetic Polymers
 Polyurethane Transdermal patch backing, blood
 Poly (acrylic acid) Cosmetic, pharmaceuticals, pump, artificial heart, and vascular grafts, foam
immobilization of cationic drugs, base for Carbopol in biomedical and industrial products.
polymers.
 Polyisobutylene Pressure sensitive adhesives for
 Poly (ethylene oxide) Coagulant, flocculent, very high transdermal delivery.
molecular‐weight up to a few millions, swelling
 Polycyanoacrylate Biodegradable tissue
agent.
adhesives in surgery, a drug carrier in nano‐ and
 Poly (ethylene glycol) Mw <10,000; liquid (Mw microparticles.
<1000) and wax (Mw >1000), plasticizer, base for
 Poly (vinyl acetate) Binder for chewing gum.
suppositories.
 Poly (vinyl chloride) Blood bag, and tubing.
 Poly (vinyl pyrrolidone) Used to make betadine
(iodine complex of PVP) with less toxicity than iodine,  Polyethylene Transdermal patch backing for drug
plasma replacement, tablet granulation. in adhesive design, wrap, packaging, containers.
 Poly (vinyl alcohol) Water‐soluble packaging, tablet  Poly (methyl methacrylate) Hard contact lenses.
binder, tablet coating.
 Poly (hydroxyethyl methacrylate) Soft contact
lenses.

CLASSIFICATION POLYMERS Diffusion
Basis on interaction with water Diffusion occurs when a drug or other active agent passes
through the polymer that forms the controlled‐release
 Non‐biodegradable hydrophobic Polymers:‐ E.g.
device. Diffusion occurs when the drug passes from the
Polyvinyl chloride,
polymer matrix into the external environment. As the
 Soluble Polymers:‐ E.g. HPMC, PEG release continues its rate normally decreases with this
type of system since the active agent has a progressively
 Hydro gels:‐ E.g. Polyvinyl pyrrolidine
longer distance to travel and therefore requires a longer
Based on polymerisation method diffusion time to release. In these systems, the
combinations of polymer matrices and bioactive agents
 Addition Polymers:‐ E.g. Alkane Polymers
chosen must allow for the drug to diffuse through the
 Condensation polymers:‐ E.g. Polysterene and pores or macromolecular structure of the polymer upon
Polyamide introduction of the delivery system into the biological
environment without inducing any change in the polymer
Based on polymerization mechanism
itself.25
 Chain Polymerization
Degradation
 Step growth Polymerization
Biodegradable polymer degrades within the body as a
Based on chemical structure result of natural biological processes, eliminating the
need to remove a drug delivery system after release of
 Activated C‐C Polymer
the active agent has been completed. Most
 Inorganic polymers biodegradable polymers are designed to degrade as a
 Natural polymers result of hydrolysis of the polymer chains into biologically
acceptable and progressively smaller compounds.26 For
Based on occurrence some degradable polymers, most notably the
 Natural polymers:‐ E.g. 1. Proteins‐collagen, polyanhydrides and polyorthoesters, the degradation
keratin, albumin, cellulose occurs only at the surface of the polymer, resulting in a
release rate that is proportional to the surface area of the
 Synthetic polymers:‐ E.g. Polyesters, polyamides drug delivery system
Based on bio‐stability Swelling
 Bio‐degradable They are initially dry and when placed in the body will
 Non Bio‐degradable absorb water or other body fluids and swell. The swelling
increases the aqueous solvent content within the
Characteristics of an ideal polymer formulation as well as the polymer mesh size, enabling
 It should be versatile and possess a wide range the drug to diffuse through the swollen network into the
of mechanical, physical, chemical properties. external environment. 27
 It should be non‐toxic and have good mechanical POLYMERS IN PHARMACEUTICAL DRUG DELIVERY
strength and should be easily administered. SYSTEM
 It should be inexpensive and easy to fabricate. Rosin
 It should be inert to host tissue and compatible Rosin a film‐forming biopolymer and its derivatives have
with environment. been extensively evaluated pharmaceutically as film‐
coating and microencapsulating materials to achieve
Criteria followed in polymer selection sustained drug release. They are also used in cosmetics,
 The polymer should be soluble and easy to chewing gums, and dental varnishes. Rosin has been used
synthesis. to prepared spherical microcapsules by a method based
on phase separation by solvent evaporation. Rosin
 It should have finite molecular weight. combination with polyvinyl pyrrolidone and dibutyl
 It should be compatible with biological phthalate (30 % w/w) produces smooth film with
environment. improved elongation and tensile strength.28‐30
 It should be biodegradable. Chitin and Chitosan
 It should provide good drug polymer linkage. Chitin a naturally abundant muco polysaccharide and

consist of 2‐acetamido‐2‐ deoxy‐b‐D‐glucose. Chitin can
General mechanism of drug release from polymer be degraded by chitinase. Chitosan is a linear
There are three primary mechanisms by which active polysaccharide composed of randomly distributed β‐(1‐
agents can be released from a delivery system namely 4)‐linked D‐glucosamine (deacetylated unit) and N‐acetyl‐


D glucosamine (acetylated unit). The most important polymerized at room temperature without production of

property of chitosan with regards to drug delivery is its condensation by‐products. These materials are
positive charge under acidic conditions. This positive hydrophobic with hydrolytic linkages that are acid‐
charge comes from protonation of its free amino groups. sensitive, but stable to base. They degrade by surface
Lack of a positive charge means chitosan is insoluble in erosion and degradation rates may be controlled by
neutral and basic environments.27 incorporation of acidic or basic excipients.
Zein POLYMERIC PLANT‐DERIVED EXCIPIENTS IN DRUG
DELIVERY SYSTEM32
Zein an alcohol‐soluble protein contained in the
endosperm tissue of Zeamais, occurs as a by‐product of Polymers have been successfully employed in the
corn processing. Zein has been employed as an edible formulation of solid, liquid and semi‐solid dosage forms
coating for foods and pharmaceuticals for decades. Zein is and are specifically useful in the design of modified
an inexpensive and most effective substitute for the fast‐ release drug delivery systems. Both synthetic and natural
disintegrating synthetic and semi synthetic film coatings polymers have been investigated extensively for this
currently used for the formulation of substrates that purpose but the use of natural polymers for
allow extrusion coating.31 pharmaceutical applications is attractive because they are
economical, readily available, non‐toxic, capable of
Collagen
chemical modifications, potentially biodegradable and
Collagen is the most widely found protein in mammals with few exceptions also biocompatible.
and is the major provider of strength to tissue. It not only
Cellulose
has been explored for use in various types of surgery,
cosmetics and drug delivery, but in bioprosthetic implants The polysaccharides of the plant cell wall consist mainly
and tissue engineering of multiple organs. of cellulose, hemicelluloses and pectin used in
pharmaceutical applications such as filler in tablets, it is
Starches
microcrystalline cellulose that represents a novel and
It is the principal form of carbohydrate reserve in green more useful cellulose powder.33 Microcrystalline cellulose
plants and especially present in seeds and underground is mainly used in the pharmaceutical industry as a
organs. Starch occurs in the form of granules (starch diluent/binder in tablets for both the granulation and
grains), the shape and size of which are characteristic of direct compression processes.32 Microcrystalline cellulose
the species, as is also the ratio of the content of the is partially depolymerised cellulose prepared by treating
principal constituents, amylose and amylopectin. A high quality cellulose with hydrochloric acid to produce
number of starches are recognized for pharmaceutical free flowing non‐fibrous particles. It was further found
use. These include maize (Zea mays), rice (Oryza sativa), that the hydroxypropylmethylcellulose matrix systems
wheat (Triticum aestivum), and potato (olanum have a stronger gel structure than those made of
tuberosum). To deliver proteins or peptidic drugs orally, Molecules polyethylene oxide, which may provide
microcapsules containing a protein and a proteinase superior in vivo performance in terms of matrix resistance
inhibitor were prepared. Starch/bovine serum albumin to the destructive forces within the gastrointestinal
mixed‐walled microcapsules were prepared using tract.34
interfacial cross‐linking with terephthaloyl chloride. The
microcapsules were loaded with native or amino‐
protected aprotinin by incorporating protease inhibitors
in the aqueous phase during the cross‐linking process.
The protective effect of microcapsules with aprotinin for
bovine serum albumin was revealed in vitro.
Polycaprolactone
Figure 2: Chemical structure of a) powdered cellulose (n
Polycaprolactone (PCL) is biodegradable polyester with a
≈ 500) or microcrystalline Cellulose (n ≈ 220) and b)
low melting point of around 60°C and a glass transition
hydroxyl propyl methyl cellulose.
temperature of about −60°C. PCL is prepared by ring
opening polymerization of ε‐caprolactone using a catalyst Pectin
such as stannous octanoate. The most common use of
Pectin is a family of complex polysaccharides present in
polycaprolactone is in the manufacture of speciality
the walls that surround growing and dividing plant cells It
polyurethanes. Polycaprolactones impart good water, oil,
is also present in the junctional zone between cells within
solvent and chlorine resistance to the polyurethane
secondary cell walls including xylem and fiber cells in
produced.
woody tissue.35, 36 Pectin has been investigated as
Polyorthoesters excipients in many different types of dosage forms such
as film coating of colon‐specific drug delivery systems
These materials have gone through several generations of
when mixed with ethyl cellulose, microparticulate
synthetic improvements to yield materials that can be
delivery systems for ophthalmic preparations and matrix

type transdermal patches. The composition of pectin can nutrition. There are three basic types of carrageenan:

vary based on the botanical source, for example pectin kappa (κ), iota (ι) and lambda (λ). The λ‐type carrageenan
from citrus contains less neutral sugars and has a smaller results in viscous solutions but is non‐gelling, while the κ‐
molecular size compared to pectin obtained from type carrageenan forms a brittle gel. The ι‐type
apples.37‐39 carrageenan produces elastic gels.45
Hydrogel beads were prepared from a mixture of cross‐
linked κ‐carrageenan with potassium and cross‐linked
alginate with calcium and they exhibited a smoother
surface morphology than that of the one‐polysaccharide
network beads. The carrageenan parts of the hydrogel
pronouncedly enhanced the thermostability of the
polymeric network. These beads were introduced as
Figure 3: Chemical structure of pectin. novel carriers for controlled drug delivery systems.46
Inulin
Inulin is resistant to digestion in the upper
gastrointestinal tract, but is degraded by colonic
microflora. Inulin with a high degree of polymerisation
was used to prepare biodegradable colon‐specific films in
combination with Eudragit® RS that could withstand
break down by the gastric and intestinal fluids. It was

shown in another study where different Eudragits® were
formulated into films with inulin that when a combination Figure 6: Chemical structure of a) λ‐carrageenan, b) ι‐
of Eudragit® RS and Eudragit® RL was mixed with inulin it carrageenan and c) κ‐carrageenan.
exhibited better swelling and permeation properties in Guar gum
colonic medium rather than other gastrointestinal
media.40, 41 Guar gum has recently been highlighted as an inexpensive
and flexible carrier for oral extended release drug
delivery.47 Guar gum is particularly useful for colon
delivery because it can be degraded by specific enzymes
in this region of the gastrointestinal tract. It is also used
as thickener for lotions and creams, as a tablet binder and
as an emulsion stabilizer.48

Figure 4: Chemical structure of inulin.
Alginates
Alginates have been used and investigated as stabilizers
in emulsions, suspending agents, tablet binders and tablet
Figure 7: Chemical structure of guar gum.
disintegrants.42 The gelling properties of alginate’s
guluronic residues with polyvalent ions such as calcium or NOVEL MUCOADHESIVE POLYMERS49
aluminium allow cross‐linking with subsequent formation
Bioadhesion can be defined as a phenomenon of
of gels that can be employed to prepare matrices, films,
interfacial molecular attractive forces amongst the
beads, pellets, microparticles and nanoparticles.43, 44
surfaces of the biological substrate and the natural or
synthetic polymers, which allows the polymer to adhere
to the biological surface for an extended period of time.50
The focus of pharmaceutical research is being steadily

shifted from the development of new chemical entities to
Figure 5: Chemical structure of alginates. the development of novel drug delivery system (NDDS) of
Carrageenans existing drug molecule to maximize their effective in
terms of therapeutic action and patent protection. The
Carrageenans is the generic name for a family of high development of NDDS has been made possible by the
molecular weight sulphated polysaccharides obtained various compatible polymers to modify the release
from certain species of red seaweeds belonging to the pattern of drug. The use of acrylate polymers for the
class Rhodophyceae, especially Chondrus crispus, development of mucoadhesive formulations have
Euchema spp, Gigartina stellata and Iridaea spp. increased many‐fold, various authors have investigated
Carrageenan extracted from seaweed is not assimilated
by the human body and provides only bulk but no

the mucoadhesive properties of different polymers with Attraction and repulsion forces arise and, for a
varying molecular architecture.51 mucoadhesive to be successful, the attraction forces must
dominate. The mechanism of mucoadhesion is generally
The use of a mucoadhesive polymer that attach to related
divided in two steps, the contact stage and the
tissue or to the surface coating of the tissue for the
consolidation stage (shown in figure 8)
targeting various absorptive mucosa such as ocular, nasal,
pulmonary, buccal, vaginal etc. This system of drug
delivery is called as mucoadhesive drug delivery system.
The various mucoadhesive polymers used for the
development of buccal delivery systems include
cyanoacrylates, polyacrylic acid, sodium
carboxymethylcellulose, hyaluronic acid,
hydroxypropylcellulose, polycarbophil, chitosan and
gellan.52, 53
Lectins Figure 8: The two steps of the mucoadhesion process
Lectins are proteins which have the ability to reversibly FUTURE TRENDS
bind with specific sugar / carbohydrate residues and are
Despite the excessive use of synthetic polymers the need
found in both animal and plant kingdom in addition to
for natural biodegradable polymers to deliver drugs
various microorganisms.54‐56 Lectins extracted from
continues to be area of active research. Natural polymer
legumes have been widely explored for targeted delivery
has numerous advantages over synthetic ones as being
systems. The various lectins which have shown specific
readily available relatively inexpensive, natural products
binding to the mucosa include lectins extracted from Ulex
of living organisms, possibilities of chemical
europaeus I, soybean, peanut and Lens culinarius.57 The
modifications. The most exciting opportunities in polymer
use of wheat germ agglutinin has been on the rise due to
drug delivery lie in the arena of responsive delivery
its least immunogenic reactions, amongst available
systems, with which it will be possible to deliver in
lectins, in addition to its capability to bind to the
response to a measured blood level or to deliver a drug
intestinal and alveolar epithelium and hence could be
precisely to a targeted site. Much of the development of
used to design oral and aerosol delivery systems.58
novel materials in controlled drug delivery is focusing on
Thiolated polymers the preparation and use of these responsive polymers
with specifically designed macroscopic and microscopic
These are the special class of multifunctional polymers
structural and chemical features.
called thiomers which are modified existing polymers by
the addition of thiol group. These are hydrophilic Such systems include:
macromolecules exhibiting free thiol groups on the
 Copolymers with desirable
polymeric backbone. Thiomers are capable of forming
hydrophilic/hydrophobic interactions.
intra‐ and interchain disulphide bonds within the
polymeric network leading to strongly improved cohesive  Complexation networks responding via hydrogen
properties and stability of drug delivery systems such as or ionic bonding.
matrix tablets. Due to the formation of strong covalent
 Polymers as nanoparticles for immobilization of
bonds with mucus glycoproteins, thiomers show the
enzymes, drugs, peptides, or other biological
strongest mucoadhesive properties of all so far tested
agents.
polymeric excipients via thioldisulphide exchange
reaction and an oxidation process. Various thiolated  New biodegradable polymers.
polymers include chitosan–iminothiolane, poly(acrylic
acid)–cysteine, poly(acrylic acid)–homocysteine,  New blends of hydrocolloids and carbohydrate‐
chitosan–thioglycolic acid, chitosan–thioethylamidine, based polymers.
alginate–cysteine, poly(methacrylic acid)–cysteine and Design and synthesis of novel combinations of polymers
sodium carboxymethylcellulose–cysteine.59 will expand the scope of new drug delivery systems in the
Poloxomer future. This will obviously require assimilation of a great
deal of emerging information about the chemical nature
Poloxomer gels have been investigated as they are and physical structure of these new materials. There is an
reported to show phase transitions from liquids to increasing movement of scientists and engineers who are
mucoadhesive gels at body temperature and will dedicated to minimizing the environmental impact of
therefore allow in‐situ gelation at the site of interest. polymer composite production. Life cycle assessment is of
MECHANISMS OF MUCOADHESION60 paramount importance at every stage of a product's life,
from initial synthesis through to final disposal and a
The mucoadhesive must spread over the substrate to sustainable society needs environmentally safe materials
initiate close contact and increase surface contact, and processing methods.61, 62
promoting the diffusion of its chains within the mucus.

CONCLUSION 13. Park, K. and Robinson, J.R., Bioadhesive polymers as
platforms for oral‐controlled drug delivery: method to
Polymer‐based pharmaceuticals are starting to be seen as study bioadhesion, Int. J. Pharm., 19, 1984, 107.
key elements to treat many lethal diseases that affect a
14. Chang, H.S., Bioadhesive polymers as platforms for oral
great number of individuals such as cancer or hepatitis.
controlled drug delivery II: synthesis and evaluation of
Although excipients have traditionally been included in
some swelling, water‐insoluble bioadhesive polymers, J.
formulations as inert substances to mainly make up Pharm. Sci., 74(4), 1985, 399.
volume and assist in the manufacturing process, they are
increasingly included in dosage forms to fulfil specialized 15. Harris, D., Fell, J.T., Sharma, H.L., and Taylor, D.C.,
Gastrointestinal transit of potential bioadhesive
functions for improved drug delivery because many new
formulations in man: a scintigraphic study, J. Controlled
drugs have unfavourable physicochemical and
Release, 12, 1990, 45.
pharmacokinetic properties. The synthetic polymers can
be designed or modified as per requirement of the 16. Leung, S.‐H.S. and Robinson, J.R., Polymer structure
formulation by altering polymer characteristics and on features contributing to Mucoadhesion II., J. Controlled
Release, 12, 1990, 187.
the other hand natural pharmaceutical excipients are
biocompatible, non toxic, environment friendly and 17. Timmermans, J. and Moes, A.J., How well do floating
economical. Several polymers have been successfully dosage forms float? Int. J. Pharm., 62, 1990, 207.
used and others are being investigated as excipients in 18. Whitehead, L., Floating dosage forms: an in‐vivo study
the design of dosage forms for effective drug delivery. demonstrating prolonged gastric retention, J. Controlled
Release, 55, 1998, 3.
REFERENCES
19. Marler, J.J., Upton, J., Langer, R., and Vacanti, J.P.,
1. Vicky V. Mody, Introduction to Polymeric Drug Delivery,
Transplantation of cells in matrices for tissue regeneration,
Internet Journal of Medical Update, 5(2): 2010 July;1‐2.
Adv. Drug Delivery Rev., 33, 1998, 165.
2. Omanathanu Pillai, Ramesh, Polymers in drug delivery,
20. Wang, D., Cathepsin K inhibitor‐polymer conjugates:
Current Opinion in chemical biology, Vol 5, issue 4, 2001,
potential drugs for the treatment of osteoporosis and
447‐451.
rheumatoid arthritis, Int. J. Pharm., 277(1–2), 2004, 73.
3. Omanathanu Pillai, Ramesh, Polymers in drug delivery,
21. Reja M, Quadir MA, Haider SS. Comparative evaluation of
Current Opinion in chemical biology, Vol 5, issue 4, 2001,
plastic, hydrophobic and hydrophilic polymers as matrices
447‐451.
for controlled release drug delivery, J Pharm Sci 692, 2003,
4. Clochard M, Dinand E, Rankin S, Simic S, Brocchini S, New 274‐291.
strategies for polymer development in pharmaceutical
22. Verhoeven, J, Controlled‐release formulations, a
science‐a short review, J Pharm Pharmacol, 2001,
hydrophilic matrix containing furosemide, Int. J. Pharm, 45,
53(9),1175‐ 1184.
1988, 65‐69.
5. Vyas SP, Khar RK. Controlled Drug Delivery: Concepts and
23. Ankita Raizada, Polymers In Drug Delivery: A Review, IJPRD,
Advances. I st ed. Vallabh prakashan, New Delhi,2002,
2(8),2010, 9‐20.
156‐189.Kathryn E. Uhrich ,Scott M. Cannizzaro , Robert S.
Langer, Polymeric Systems for Controlled Drug Release, 24. Nokano M, Ogata A, In vitro release characteristics of
Chem. Rev, 99, 1999, 3181‐3198. matrix tablets, Study of Karaya gum and Guar gum as
releasemodulators, Ind. J. Pharm. Sc, 68, 6, 2006, 824‐826.
6. Reja M, Quadir MA, Haider SS, Comparative evaluation of
plastic, hydrophobic and hydrophilic polymers as matrices 25. Poddar RK, Rakha P, Singh SK, MishraDN, Bioadhesive
for controlledrelease drug delivery, J Pharm Sci 692, 2003, Polymers as a Platform for Drug Delivery: Possibilities and
274‐291. Future Trends, Research J on Phamacetical Dosage Form
and Technology, 2,1,2010, 40‐54.
7. Taylor and Francis, Polymers in Drug Delivery System, 2006,
1‐236. 26. Kiran Sharma, Natural biodegradable polymers as matrices
in transdermal drug delivery, Int. J. Drug Dev. & Res., April‐
8. Hoffman, A.S., Hydrogels for biomedical applications, Adv.
June 3 (2): 2011, 85‐103
Drug Delivery Rev.54, 2002, 3–12.
27. Satturwar, P.M.; Fulzele, S.V.; Dorle, A.K. Biodegradation
9. Park, J.H., Ye, M.L., and Park, K., Biodegradable polymers
and in vivo biocompatibility of rosin: a natural film‐forming
for microencapsulation of drugs, Molecules, 10, 146–161,
polymer. AAPS PharmSciTech. 4, 2003, 1‐6.
2005.
28. Mandaogade, P.M.; Satturwar, P.M.; Fulzele, S.V.; Gogte,
10. Almeida, Biomedical application of polymer based
B.B.; Dorle, A.K. Rosin derivatives: novel film forming
pharmaceuticals, Biomedical Engineering – Group XII,2008.
materials for controlled drug delivery. Reactive Funct.
11. Van Savage, G. and Rhodes, C.T., The sustained release Polym. 50, 2002, 233‐243.
coating of solid dosage forms: a historical review, Drug Dev.
29. Fulzele, S.V.; Satturwar, P.M.; Dorle, A.K. Study of the
Industrial Pharm., 21(1), 1995, 93.
biodegradation and in vivo biocompatibility of novel
12. Longer, M.A., Ch’ng, H.S., and Robinson, J.R., Bioadhesive biomaterials. Eur. J. Pharm. Sci. 20, 2003, 53‐61.
polymers as platforms for oral controlled drug delivery III:
oral delivery of chlorothiazide using a bioadhesive polymer,
J. Pharm. Sci., 74(4), 1985, 406.


30. Elisangela C, Antonio J, Antonio A, Jose A, Luiz H, 47. Coviello, T.; Alhaique, F.; Dorigo, A.; Matricardi, P.; Grassi,
Preparation and characterization of thermoplastic M. Two galactomannans and scleroglucan as matrices for
starch/zein blends, Mat. Res., 10, 3, 2007, 1516‐ 1439. drug delivery: Preparation and release studies. Eur. J.
Pharm. Biopharm. 66,2007, 200‐209.
31. Carien E. Beneke, Polymeric Plant‐derived Excipients in
Drug Delivery, Molecules 14,2009, 2602‐2620 48. Mythri.G, Novel Mucoadhesive Polymers–A Review, Journal
of Applied Pharmaceutical Science 01 (08); 2011: 37‐42
32. Malafaya, P.B.; Silva, G.A.; Reis, R.L. Natural‐origin
polymers as carriers and scaffolds for biomolecules and cell 49. Duchene D, Touchard F and Peppas N A. Pharmaceutical
delivery in tissue engineering applications. Adv. Drug Deliv. and medical aspects of Bioadhesive system for drug
Rev. 59, 2007, 207‐233. administration. Drug Dev. Ind. Pharm., 14, 1998, 283‐381.
33. Jamzad, S.; Fassihi, R. Development of a controlled release 50. Smart J D, Kellaway I W and Worthington H E C. An in vitro
low dose class II drug‐Glipizide. Int. J. Pharm. 312,2006, 24‐ investigation of mucosa adhesive materials for use in
32. controlled drug delivery. J. Pharm. Pharmacol., 36, 1984,
pp. 295‐299.
34. Ridley, B.L.; O’Neill, M.A.; Mohnen, D. Pectins: structure,
biosynthesis and oligogalacturonide related signaling. 51. Andrew G P, Laverty T P and Jones D S. Mucoadhesive
Phytochemistry. 57, 2001, 929‐967. polymeric for controlled drug delivery. European Journal of
Pharmaceutics and Biopharmaceutics, 71 (3), 2009, 505‐
35. Mohnen, D. Pectin structure and biosynthesis. Curr. Opin.
518.
Plant Biol. 11, 2008, 266‐277.
52. Remuñán‐López C, Portero A, Vila‐Jato J L, Alonso M J.
36. Fry, S.C. Primary cell wall metabolism, tracking the careers
Design and evaluation of chitosan/ethylcellulose
of wall polymers in living plant cells. New Phytol. 161,2004,
mucoadhesive bilayered devices for buccal drug delivery.
641‐675.
Journal of Controlled Release. 55 (2‐3), 1998, pp. 143‐152.
37. Sriamornsak, P.; Thirawong, N.; Weerapol, Y.; Nunthanid,
53. Lehr C M. Lectin‐mediated drug delivery: the second
J.; Sungthongjeen, S. Swelling and erosion of pectin matrix
generation of bioadhesives. J. Control. Release, 65, 2000,
tablets and their impact on drug release behavior. Eur. J.
pp. 19– 29.
Pharm. Biopharm. 67, 2007, 211‐219.
54. Haltner E, Easson J H and Lehr C M. Lectins and bacterial
38. Cárdenas, A.; Goycoolea, F.M.; Rinaudo, M. On the gelling
invasion factors for controlling endo and transcytosis of
behaviour of ‘nopal’ (Opuntia ficus indica) low metholoxyl
bioadhesive drug carrier system. Euro. J. Pharm. Biopharm,
pectin. Carbohydr. Polym. 73, 2008, 212‐222.
44, 1997, pp. 3‐13.
39. Vervoort, L.; Kinget, R. In vitro degradation by colonic
55. Smart J D. Lectin‐mediated drug delivery in the oral cavity.
bacteria of inulinHP incorporated in Eudragit RS films. Int. J.
Advanced Drug Delivery Reviews. 56 (4), 2004, pp. 481‐489.
Pharm. 129, 1996, 185‐190.
56. Hietanen J and Salo O P. Binding of four lectins to normal
40. Vervoort, L.; Van den Mooter, G.; Augustijns, P.; Kinget, R.
human oral mucosa. European Journal of Oral Sciences, 92
Inulin hydrogels. I. Dynamic and equilibrium swelling
(5), 2007, pp. 443 – 447.
properties. Int. J. Pharm. 172, 1998, 127‐135.
57. Sharma A, Sharma S and Khuller G K. Lectin‐functionalized
41. Sudhakar, Y.; Kuotsu, K.; Bandyopadhyay, A.K. Buccal
poly (lactide‐co‐glycolide) nanoparticles as oral/aerosolized
bioadhesive drug delivery – A promising option for orally
antitubercular drug carriers for treatment of tuberculosis.
less efficient drugs. J. Control. Release 114, 2006, 15‐40.
The Journal of Antimicrobial Chemotherapy, 54 (4), 2004,
42. Sarmento, B.; Ribeiro, A.; Veiga, F.; Sampaio, P.; Neufeld, pp. 761‐766.
R.; Ferreira, D. Alginate/Chitosan nanoparticles are
58. S. Roy, Polymers in Mucoadhesive Drug Delivery System: A
effective for oral insulin delivery. Pharm. Res. 24,2007,
Brief Note, designed monomer and polymer 12 (2009),
2198‐2206.
483‐495.
43. Ching, A.L.; Liew, C.V.; Heng, P.W.S.; Chan, L.W. Impact of
59. Saravana Kumar, Polymers in Mucoadhesive Microsphere
cross‐linker on alginate matrix integrity and drug release.
Drug Delivery System Review, JGTPS July‐September ‐ Vol.2
Int. J. Pharm. 355, 2008, 259‐268.
(3), 2011, 249‐263.
44. Nerurkar, J.; Jun, H.W.; Price, J.C.; Park, M.O. Controlled‐
60. Raj Kumar Poddar, Pankaj Rakha, SK Singh and DN Mishra,
release matrix tablets of ibuprofen using cellulose ethers
Bioadhesive Polymers as a Platform for Drug Delivery:
and carrageenans: effect of formulation factors on
Possibilities and Future Trends, Research J on
dissolution rates. Eur. J. Pharm. Biopharm. 61, 2005, 56‐68.
Pharmaceutical Dosage Form and Technology, 2,1,
45. Mohamadnia, Z.; Zohuriaan‐Mehr, M.J.; Kabiri, K.; Jamshidi, 2010,40‐54.
A.; Mobedi, H. Ionically cross‐linked carrageenan‐alginate
61. Ebihara., Controlled release formulations to increase the
hydrogel beads. J. Biomater. Sci. Polymer Edn. 19, 2008, 47‐
bioadhesive properties, Drug Res, 33,1983, 163.
59.

46. Varshosaz, J.; Tavakoli, N.; Eram, S.A. Use of natural gums
and cellulose derivatives in production of sustained release
Metoprolol tablets. Drug Deliv. 13,2006, 113‐119.

*********************


Polymers in Pharmaceutical Drug Delivery System: A Review

Загружено:

Сведения о документе

Оригинальное название

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

Polymers in Pharmaceutical Drug Delivery System: A Review

Загружено:

Авторское право:

Доступные форматы

Int. J. Pharm. Sci. Rev. Res.

INTRODUCTION compartments. These technical development in drug

International Journal of Pharmaceutical Sciences Review and Research Page 57

forms results in suboptimal therapy and/or systemic side processes including proliferation and differentiation. It

International Journal of Pharmaceutical Sciences Review and Research Page 59

easily produced in substantial quantities. It appears that Cellulose‐Based Polymers

 It should provide good drug polymer linkage. Chitin a naturally abundant muco polysaccharide and

International Journal of Pharmaceutical Sciences Review and Research Page 61

D glucosamine (acetylated unit). The most important polymerized at room temperature without production of

type transdermal patches. The composition of pectin can nutrition. There are three basic types of carrageenan:

The focus of pharmaceutical research is being steadily

International Journal of Pharmaceutical Sciences Review and Research Page 65

International Journal of Pharmaceutical Sciences Review and Research Page 66

Вам также может понравиться